The nuclear receptor family is made up of ligand-activated transcriptional regulators that have been implicated as key regulators of development and metabolic homostatsis of the human body. Many common diseases such as atherosclerosis, hepatic and pulmonary fibrosis, cancer and chronic inflammation have their origins in loss metabolic or developmental control. We will focus on exploring the mRNA expression profile of nuclear hormone receptors in human diseases including but not limited to nonalcoholic steatohepatitis (NASH), atherosclerosis and diabetes, skin diseases (eg psoriasis), brain tumors and myeloid leukemia. In addition, selective mouse models will be used to examine the expression pattern of mRNA NR family during early and late phases of progression of metabolic and inflammation diseases such as atherosclerosis. Profiling will be achieved through the quantitative PCR NR NURSA platform which provides a sensitive and highly quantitative method for analyzing NR mRNA levels. The data collected from these studies will be contained within a shared Bioinformatics Resource for data mining by the wider scientific community. In addition one of the major goals of this project is to develop of new analytical tools for determining and altering the expression of all members of the nuclear receptor family in specific cells and tissues. In addition, we will design, develop and validate a comprehensive lentiviral shRNA knockdown library that targets the entire NR family. Finally, we will use the library to interrogate cell lines and animal models of metabolic, inflammatory and cancer states in which a receptor has been shown to have a dynamic and/or dominant expression profile. The NR lentiviral shRNA knockdown library will be made available other NURSA members with the eventual goal of supplying the research community with a powerful new tools for analyzing NR function.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Program--Cooperative Agreements (U19)
Project #
Application #
Study Section
Special Emphasis Panel (ZDK1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Baylor College of Medicine
United States
Zip Code
Kim, Kang Ho; Choi, Sungwoo; Zhou, Ying et al. (2017) Hepatic FXR/SHP axis modulates systemic glucose and fatty acid homeostasis in aged mice. Hepatology 66:498-509
Fleet, Tiffany; Stashi, Erin; Zhu, Bokai et al. (2016) Genetic and Environmental Models of Circadian Disruption Link SRC-2 Function to Hepatic Pathology. J Biol Rhythms 31:443-60
Wagner, Martin; Choi, Sungwoo; Panzitt, Katrin et al. (2016) Liver receptor homolog-1 is a critical determinant of methyl-pool metabolism. Hepatology 63:95-106
Han, Sang Jun; Begum, Khurshida; Foulds, Charles E et al. (2016) The Dual Estrogen Receptor ? Inhibitory Effects of the Tissue-Selective Estrogen Complex for Endometrial and Breast Safety. Mol Pharmacol 89:14-26
Han, Sang Jun; Jung, Sung Yun; Wu, San-Pin et al. (2015) Estrogen Receptor ? Modulates Apoptosis Complexes and the Inflammasome to Drive the Pathogenesis of Endometriosis. Cell 163:960-74
Wu, San-Pin; Kao, Chung-Yang; Wang, Leiming et al. (2015) Increased COUP-TFII expression in adult hearts induces mitochondrial dysfunction resulting in heart failure. Nat Commun 6:8245
Tang, Ke; Tsai, Sophia Y; Tsai, Ming-Jer (2015) COUP-TFs and eye development. Biochim Biophys Acta 1849:201-9
Xu, Pingwen; Cao, Xuehong; He, Yanlin et al. (2015) Estrogen receptor-? in medial amygdala neurons regulates body weight. J Clin Invest 125:2861-76
Kang, Yun Kyoung; Putluri, Nagireddy; Maity, Suman et al. (2015) CAPER is vital for energy and redox homeostasis by integrating glucose-induced mitochondrial functions via ERR-?-Gabpa and stress-induced adaptive responses via NF-?B-cMYC. PLoS Genet 11:e1005116
Kida, Yasuyuki S; Kawamura, Teruhisa; Wei, Zong et al. (2015) ERRs Mediate a Metabolic Switch Required for Somatic Cell Reprogramming to Pluripotency. Cell Stem Cell 16:547-55

Showing the most recent 10 out of 214 publications